Peripheral cholecystokinin promotes thermogenesis via vagal afferent signalling, hypothalamic oxytocin and sympathetic outflow to brown adipose tissue

neurons and OXTR signalling), and the efferent output (iBAT sympathetic nerves). This study further suggests that CCK-AR-expressing vagal sensory neurons may contribute to thermoregulation under physiological conditions in which CCK is endogenously released. KEY POINTS: Vagal sensory nerves, which connect the gut and the brain, play a key role in regulating meal-related physiology; however, their role in thermoregulation remains incompletely understood. This study reveals that i.p. cholecystokinin (CCK)-induced thermogenesis involves functional neural components, including the afferent input (CCK-A receptor-expressing vagal afferents), the central integrative hub (hypothalamic oxytocin neurons in the paraventricular nucleus and oxytocin receptor-expressing neurons in the rostral medullary raphe) and the efferent output (sympathetic nerves innervating intrascapular brown adipose tissue). This newly identified gut-brain-fat axis may contribute to part of diet-induced thermogenesis, and its impairment could be involved in the development of metabolic disorders such as obesity.